The rapid intravenous administration of digitalis has recently been shown to cause a substantial increase in coronary vascular resistance in the normal heart. This neurogenically mediated increase in coronary blood flow would be potentially detrimental if it occurred during ischemia. During the first year of funding we have evaluated the effects of intravenous acetylstrophanthidin and digoxin on coronary vascular resistance during acute global ischemia in anesthetized dogs (chloralose and urethan). Reducing coronary perfusion pressure to induce ischemia elevated left ventricular end diastolic pressure and resulted in negative myocardial lactate balance. Following intravenous acetylstrophanthidin (0.5 mg) coronary vascular resistance showed either erratic increases or progressive increases terminating in ventricular fibrillation. The increases in coronary vascular resistance appeared secondary to alpha adrenergic receptor stimulation. Erratic increases in coronary vascular resistance were also observed with intravenous digoxin during ischemia, and these increases could be abolished with alpha adrenergic receptor blockade. Thus, intravenous digitalis in the ischemic heart results in increases in coronary vascular resistance mediated through alpha adrenergic receptor stimulation which are potentially detrimental. BIBLIOGRAPHIC REFERENCE: Sagar, K., Hanson, E., and Powell, W.J., Jr.: Neurogenic Coronary Vasoconstrictor Effects of Digitalis During Acute Global Ischemia. Am. J. Cardiol. 39:261, 1977.